Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.

ABSTRACT:

Background

Non-nucleoside inhibitors of HIV reverse transcriptase are an important component of treatment against HIV infection. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation.

Methods

Molecular dynamics based free energy perturbation simulations have been run to study factors that contribute to protein-ligand binding, and the results are compared with those from previous Monte Carlo based simulations and activity data.

Results

Predictions of protein-ligand binding modes are very consistent for the two simulation methods; the accord is attributed to the use of an enhanced sampling protocol. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment.

Conclu

SUBMITTER: Cole DJ 

PROVIDER: S-EPMC4339369 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature